{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Alade AN"],"funding":["National Center for Research Resources","NCRR NIH HHS","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["716-732"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10928895"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(3)"],"pubmed_abstract":["This study evaluated the underlying mechanistic links between genetic variability in vitamin K metabolic pathway genes (<i>CYP4F2</i> and <i>CYP4F11</i>) and phylloquinone hydroxylation activity using genotype- and haplotype-based approaches. Specifically, we characterized genetic variability in the <i>CYP4F2/CYP4F11</i> locus and compared common single allele genotypes and common haplotypes as predictors of hepatic gene expression, enzyme abundance, and phylloquinone (VK<sub>1</sub>) ω-hydroxylation kinetics. We measured <i>CYP4F2</i> and <i>CYP4F11</i> mRNA levels, CYP4F2 and CYP4F11 protein abundances, and the VK<sub>1</sub> concentration-dependent ω-hydroxylation rate in matched human liver nucleic acid and microsome samples, utilizing a novel <i>in vitro</i> population modeling approach. Results indicate that accounting for the <i>CYP4F2*3</i> allele alone is sufficient to capture most of the genetic-derived variability in the observed phenotypes. Additionally, our findings highlight the important contribution that CYP4F11 makes toward vitamin K metabolism in the human liver."],"journal":["ACS pharmacology & translational science"],"pubmed_title":["Cytochrome P450 Family <i>4F2</i> and <i>4F11</i> Haplotype Mapping and Association with Hepatic Gene Expression and Vitamin K Hydroxylation Activity."],"pmcid":["PMC10928895"],"funding_grant_id":["TL1-RR025016","P01 GM116691","TL1 RR025016","P01-GM116691"],"pubmed_authors":["Alade AN","Prasad B","Claw KG","Rettie AE","Thummel KE","McDonald MG"],"additional_accession":[]},"is_claimable":false,"name":"Cytochrome P450 Family <i>4F2</i> and <i>4F11</i> Haplotype Mapping and Association with Hepatic Gene Expression and Vitamin K Hydroxylation Activity.","description":"This study evaluated the underlying mechanistic links between genetic variability in vitamin K metabolic pathway genes (<i>CYP4F2</i> and <i>CYP4F11</i>) and phylloquinone hydroxylation activity using genotype- and haplotype-based approaches. Specifically, we characterized genetic variability in the <i>CYP4F2/CYP4F11</i> locus and compared common single allele genotypes and common haplotypes as predictors of hepatic gene expression, enzyme abundance, and phylloquinone (VK<sub>1</sub>) ω-hydroxylation kinetics. We measured <i>CYP4F2</i> and <i>CYP4F11</i> mRNA levels, CYP4F2 and CYP4F11 protein abundances, and the VK<sub>1</sub> concentration-dependent ω-hydroxylation rate in matched human liver nucleic acid and microsome samples, utilizing a novel <i>in vitro</i> population modeling approach. Results indicate that accounting for the <i>CYP4F2*3</i> allele alone is sufficient to capture most of the genetic-derived variability in the observed phenotypes. Additionally, our findings highlight the important contribution that CYP4F11 makes toward vitamin K metabolism in the human liver.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-02T10:10:35.41Z","creation":"2025-04-03T23:26:37.154Z"},"accession":"S-EPMC10928895","cross_references":{"pubmed":["38481683"],"doi":["10.1021/acsptsci.3c00287"]}}